Primary antiphospholipid syndrome unusual presentation in a seventy two year old man.

A 72 year old man with a history of TIAs and stroke with unexplained moderately raised ESR presented a year later with rapid deterioration of vision in his left eye because of central retinal vein occlusion. Primary antiphospholipid syndrome is found in patients with history of arterial or venous thromboembolism, thrombocytopenia and recurrent fetal loss without features of SLE.

Case report

A seventy two year old man was referred by his GP with a history of tiredness, lethargy, stiff knees and hips and an ESR of 56 mm/hr. He gave a history of waking up with lethargy and memory loss. He was on treatment for hypercholesterolemia and he smokes 10 cigarettes a day. He had no history of headache or any other symptoms suggestive of temporal areteritis. On examination at that time he was found to be slightly overweight and had xanthelasma around his eyes. Pulse was 60/minute and regular and BP was 160/80. No carotid bruits was found and no tenderness over the temporal artery. The rest of the physical examination was normal. His ESR was 52 mm/hr. Full blood counts, LFT, TFT, Vitamin B12, Red Cell Folate, VDRL, Autoimmune screening, Myloma screen, and chest x-ray were all within normal limits. CT Scan of his brain showed small vessel ischaemia with a small lacunar infarction. In view of the systemic risk factors and the CT Scan finding he was diagnosed with cerebrovascular disease. He was started on Aspirin 75mg, Perindopril 2mg and Benzofibrate 200 mg TDS as he was intolerant to Statins.

Nine months later he presented to the eye clinic with rapid deterioration of vision in his left eye. His best corrected visual acuities were 6/9 and counting Fingers in the right and left eye respectively. He was found to have a left ischaemic central retinal vein occlusion with macular oedema (Figure 1).

Fig 1

Normal fundus

Ischaemic occlusion of left central retinal vein with macular oedema

He was referred from the eye clinic again to the physician for reassessment. Thrombophilia screen was requested to exclude the possibility of a coagulation disorder. The result showed a very high Anticardiolipin IgM [80.3 MPL u/mL] normal value should be less than 9 MPL u/mL. The test was repeated twice and still showed a high level. Further investigations requested to exclude secondary antiphospholipid syndrome were normal including ultrasound scan of the abdomen, tumour markers and colonoscopy. His entire autoimmune screen remained negative apart from his anticardiolipin antibody.

The risk of further thromboembolic complication was considered to be high. He was therefore started on long-term Warfarin treatment.

He has been under follow up for more than twelve months with no further events. His left eye showed signs of neovascular glaucoma and had full pan retinal Laser photocoagulation. His left eye remained stable during further follow up.

Discussion

We present a case of primary antiphospholipid syndrome in this patient where the diagnosis was not suspected initially because of his age and also the presence of multiple risk factors for cerebrovascular disease which has led to delay in investigating other causes of vascular thrombosis until he developed central retinal vein thrombosis. The other presenting symptom was the recent memory loss which was initially hard to explain. However, cognitive dysfunction in antiphospholipid syndrome (APS) has been partially described, despite the increased interest in this area in recent years. A number of studies of patients with SLE and healthy individuals have shown an association between positive aPL antibody findings and cognitive dysfunction [1-3]

Tektonido et al [3] studied Sixty patients (39 with primary APS and 21 with systemic lupus erythematosus–related APS) and 60 healthy individuals matched for age, sex, and education. He found Twenty five (42%) of the 60 patients with APS had cognitive deficits compared with 11 (18%) healthy control subjects. He concluded that Cognitive deficits may often be found among patients with APS, independent of any history of central nervous system involvement. Livedo reticularis and the presence of white matter lesions on brain magnetic resonance imaging are associated with an increased risk for cognitive dysfunction in APS.

Antiphospholipid syndrome is a multisystem disorder with a wide range of neurological manifestations, and occurs more commonly in young to middle aged people [4]. Retinal vascular occlusive disease occurs infrequently and considering our patient's age this makes the case unusual. Other features such as recurrent miscarriages, thrombocytopenia, and livedo reticularis, may complicate 10 to 15 per cent of patients with systemic lupus erythematosus. When these features, together with the presence of antiphospholipid antibodies (usually cardiolipin, or the lupus anticoagulant) occur in the presence of other more classical lupus features, the condition is known as secondary antiphospholipid syndrome, but they can occur on their own, in which case the patient is said to have primary antiphospholipid syndrome. Pathological effects of antiphospholipid antibodies are not due to deposition and complement activation but due to activation of thrombus formation. This leads to arterial and venous thromboses that may be particularly harmful in the cerebral and renal circulation. The mechanism by which thrombosis is altered is not fully understood; antiphospholipid antibodies found in systemic lupus erythematosus and the primary antiphospholipid antibody syndrome recognize a complex of negatively charged phospholipids with the plasma protein 2-glycoprotein 1. Antiphospholipid antibodies can be found in infectious diseases such as syphilis.

The frequency of ocular vasculo-occlusive disorders in patients with this syndrome ranges from 0.5 to 8%, with the majority affecting the retinal vasculature. Both arterial and venous systems may be involved [5-7]. Retinal vein thrombosis, deep vein thrombosis, pulmonary embolism, sagittal vein thrombosis, cerebral artery occlusion and myocardial infarction as well as other venous or arterial thrombosis at various sites have been described in patients with Antiphospholipid syndrome [8, 9] and therefore it is important to make the diagnosis at the earliest opportunity.

The therapeutic approach to Antiphospholipid syndrome is still controversial. Immunosuppressant or high doses of corticosteroids to suppress the antiphospholipid antibodies have not proved to be sufficient. The management of acute thrombotic complications of Antiphospholipid syndrome is similar to the management in other clinical settings. However, patients with this syndrome are more prone to recurrent thrombotic events [10] therefore long term warfarin treatment is recommended.

Key points

Presence of multiple risk factors for stroke should not discourage doctors from looking for other causes of thrombosis

Long term Warfarin treatment should be considered to reduce the recurrence of thrombotic events.